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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

 ​ The test substance is covered by a category approach of methylenediphenyl diisocyanates (MDI) with existing data gaps filled according to ECHA guidance on Read Across (ECHA, 2017).  Hence, data of the category substances can be used to cover this endpoint. The read-across category justification document is attached in. It is important to note that the MDI category approach for read-across of environmental and human hazards between the MDI substances belonging to the MDI category is work in progress under REACH. Therefore the document should be considered a draft.  In this category Substances of the MDI category all share similar chemical features namely that they a) all contain high levels of mMDI, and b) contain have at least two aromatic NCO groups that are electronically separated from other aromatic rings by at least a methylene bridge. It is the NCO value (driven by the bioaccessible NCO groups on relatively soluble mMDI and low molecular weight species (e.g. three-ring oligomer) which is responsible for chemical and physiological reactivity and subsequent toxicological profile. The substances 4,4’-MDI, 4,4’-MDI/DPG/HMWP and pMDI are identified as the boundary substances within this MDI category. These three substances represent the extremes of key parameters (i.e. mMDI content and NCO value) within the MDI category that determine the hypothesized Mode of Action (MoA). Although NCO groups are present on the higher molecular weight constituents, they do not contribute to the toxicity profile because they are hindered due to their increased size and hydrophobicity.


All substances of the MDI category have a potential to be skin sensitizers due to the presence of reactive NCO groups. However, due to rapid reaction with superficial skin proteins (e.g. keratin) and moisture on the skin which leads to the formation of insoluble masses (see Chapter 3.1.2), dermal penetration is limited. This is consistent with the negative Buehler assay (in which the skin is intact as opposed to intradermal assays) and with the low prevalence of contact allergy reflected under documented human evidence. Based on the reactivity demonstrated for all category substances, there is high confidence in the assessment as contact allergens and no need for further testing.

The available research and test data are consistent with the hypothesized MoA in which the NCO group on the mMDI reacts with biological nucleophiles i.e. protein and drives the MIE and subsequent sequence of KEs leading to the acquisition of MDI-mediated sensitization. The human experience clearly indicates that monomeric MDI isomers and oMDI are not strong skin sensitizers, and in accordance with Regulation (EU) No 286/2011 MDI is classified as Category 1 skin sensitizer. As all substances of the MDI category have a high mMDI content, they are expected to have similar sensitization properties in the skin. This is consistent with the available data on four substances of the MDI category. 


Substances of the MDI category have been demonstrated to result in sensitization in classic in vivo assays for contact allergy. For substances of the MDI category, reliable studies using the Buehler method and the Guinea Pig Maximization Test (GPMT) are available and demonstrate that they are a skin sensitizer. 

More recently, the local lymph node assay (LLNA) has been used to evaluate potency. In studies marked as supporting studies under REACH, two mouse local lymph node assays (Dearman et al., 1992; Hilton et al., 1995), demonstrated the skin sensitisation potential of MDI substances. Dearman et al. found an EC3 between equal or greater than 0.25 and less than 0.5, with a Stimulation Index (SI) between 1.54 and 84.53, and Hilton et al. (1995) found an EC3 of less than 0.03 with a SI between 3.45 and 30.76. 

The ‘Monomeric MDI’ subgroup

2,2’-MDI was tested in a modified non-radioactive LLNA in female mice according to OECD TG 429 (Vohr, 2011). Concentrations of 0 % (vehicle control), 2 %, 10 % and 50 % formulated in acetone/olive oil (4:1) were tested. Compared to vehicle-treated animals there was a significant increase regarding the weights of the draining lymph nodes and the cell counts in all dose groups. The corresponding cell count stimulation indices were 3.10, 2.60 and 3.00, respectively. The positive cut-off level was set at cell count stimulation index of 1.4. An EC1.4 was not reported and cannot be estimated retrospectively as the stimulation indices exceeded 1.4 at all test substance concentrations. A significant increase compared to vehicle treated animals regarding ear swelling and ear weights was detected in all dose groups. An increase in this parameter would point to an acute irritant (inflammatory) response. However, such an irritant property can augment the skin sensitizing potential of a test compound. The results show that 2,2’-MDI has a strong sensitizing potential in mice after dermal application.

For 4,4’-MDI, three animal studies are available, each of which is assigned a Klimisch rating of 2. The study marked as key study under REACH was performed similar to OECD Guideline 406 according to the Buehler method in guinea pigs (Davis et al., 1984). This study demonstrated that at epicutaneous occlusive induction doses of 0.25 %, 0.75 %, and 2.5 %, some animals exhibited marginal responses to high challenge concentrations of the test material (challenge concentrations: 0.00075 %, 0.0075 %, 0.075 %, 0.25 %, and 0.75 %). However, only one definitive response (score of 1) was seen at a low induction dose to the mid-high challenge concentration. Based on the lack of dose-response and the overall marginal and inconsistent results the no-effect level of this study was defined as 100 mM (2.5 %), which can be seen as a threshold under the test conditions used.

Studies marked as supporting studies under REACH, two mouse local lymph node assays (LLNA) (Dearman et al., 1992; Hilton et al., 1995), demonstrated a sensitisation potential of 4,4’-MDI. Dearman et al. found an EC3 between equal or greater than 0.25 and less than 0.5, with a SI between 1.54 and 84.53, and Hilton et al. found an EC3 of less than 0.03 with a of SI between 3.45 and 30.76.

The ‘MDI and its condensation products’ subgroup

4,4'-MDI homopolymer was evaluated in a guinea pig maximization test according to OECD 406 (Mallory, 2009f). Prior to experimental initiation of the induction, the irritation potential of the test article was determined with a dose range-finding studies (intradermal and topical) utilizing eleven naive guinea pigs. Based upon these results, the intradermal dose utilized was 0.5 %, the topical induction dose was 50 % and the challenge dose utilized was 20 % in the main study. Under the conditions of this study, an intradermal induction of 4,4'-MDI homopolymer at 0.5 % with a topical induction at 50 %, followed by a topical challenge at 20 % to guinea pigs did elicit a dermal sensitization response at 24 and 48 hours post treatment. Therefore, 4,4'MDI homopolymer is considered a contact sensitizer in Guinea Pigs.

The ‘MDI and its reaction products with glycols’ subgroup

An additional guinea pig maximization test according to OECD 406 is available for 4,4’-MDI/DPG (Mallory, 2009g). In this study, an intradermal induction of the test material at 0.5% with a topical induction at 75 %, followed by a topical challenge at 25 % to guinea pigs elicited a dermal sensitization response at 24 or 48 hours post treatment in 10 of 10 animals. Based on these results, the test substance is considered sensitizing to the skin in guinea pigs.


Human information

Several case reports are available that describe allergic contact dermatitis in individuals exposed to 4,4’-MDI.

Bruynzeel and van der Wegen-Keijser (1993) reported allergic contact dermatitis in a cast technician working with a fiberglass-reinforced PU cast which contained “isocyanate-terminated prepolymer” and 4,4’-MDI. In patch tests, she was allergic to MDA, but did not respond to 4,4’-MDI.

Liden (1980) reported allergic dermatitis in a woman who regularly prepared MDI-based PU molds during her work in a clinic. Her unprotected forearms were exposed during the mixing of an 4,4’-MDI-containing product with the polyol compound.


Estlander et al. (1992) summarized six cases of allergic contact dermatitis diagnosed between 1974 and 1990 in individuals occupationally exposed to different diisocyanates (including 4,4’-MDI) and other polyurethane chemicals. On patch testing, five individuals were allergic to 4,4’-MDI and MDA, four were additionally allergic to TDI, and three additionally were allergic to aliphatic diisocyanates, i.e. IPDI, TMDI and HDI. One patient responded to MDA only, which the authors indicated may be due to primary sensitization to MDA and cross-allergy to 4,4’-MDI.


In addition, two epidemiological studies describe allergic skin reactions in workers exposed to MDI substances.

Bernstein et al. (1993) conducted a cross-sectional study of 243 workers (100 % of the workforce) exposed to MDI substances (not further specified) in a polyurethane mould plant that had been designed to minimize MDI substances exposure. Levels of MDI substances were continuously monitored and maintained below 0.05 mg/m³. All participants were screened by questionnaire and tested for serum antibodies to MDI-HSA (MDI-human serum albumin). Of the 243 workers tested, only two had elevated levels of both serum specific IgE and IgG to MDI-HSA. Both had worked in the finishing area for at least two years, where they applied MDI resin mixtures to mend imperfections in the final product. One of the latter aforementioned workers reported immediate-onset urticaria and facial angioedema that began three months after he began mixing the MDI resin mixture in the finishing area. He denied MDI-associated respiratory symptoms and was the only worker to exhibit epicutaneous reactivity to MDI-HSA (5 mg/mL). Because respiratory symptoms and peak expiratory flow rate abnormalities were absent in this case, it may be that the skin was the primary route of sensitisation. The other worker was free of symptoms and had a negative result on skin prick testing to MDI-HSA.

A new syndrome of MDI-induced cutaneous anaphylaxis was recognized in this survey, which suggested that strict control of ambient diisocyanate exposure did not prevent the rare occurrence of IgE-mediated sensitisation through the skin.


In an epidemiological study of occupational dermatitis in five different shoe factories, 246 workers were interviewed, examined and patch tested using standard and occupational patch test series (Mancuso et al., 1996). In two workers with allergic contact dermatitis, sensitisation to 4,4’-MDI was detected. One of two workers reacted simultaneously to both 4,4’-MDI and MDA. The other one reacted only to 4,4’-MDI.

Schlede et al. (2003) published the conclusions of a panel consisting of 30 experts in the field of skin sensitization on the potency of 244 chemicals in terms of their skin sensitization potential. Clinical and experimental data on humans and results of animal tests as documented in the scientific literature were carefully collected and evaluated, and the 244 substances were ranked by assigning them to one of three categories. The most potent contact allergens were ranked in Category A (significant allergenic properties), substances with a solid-based indication of a contact allergenic potential and substances with the capacity of cross-reactions were listed in Category B, and substances with insignificant or questionable allergenic effects were listed in Category C. 4,4’-MDI was allocated to Category B based on the following criteria:

  • Less frequently proven contact allergenic effect in humans considering existing positive animal data

  • The capacity of substances to induce cross-reactions in humans without being a significant allergen itself


 Short description of key information: 


MDI is a skin sensitiser based on animal and human data. In consideration of human case reports and epidemiological studies the skin sensitising potential of MDI can be regarded as not strong.


 Justification for selection of skin sensitisation endpoint: 


Study with quality assurance and reliability 2, conducted according to the Buehler Method in guinea pigs




Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

While no generally accepted and validated test system is available to investigate the sensitizing effects of substances on the respiratory tract, numerous animal studies are available to demonstrate the respiratory sensitizing potential of MDI, mostly in guinea pigs and rats. These studies are summarized in the category justification document, IUCLID Annex III Overall, the main findings of these animal studies are the following:

  • exposure to MDI by inhalation, but also via the dermal route, can induce respiratory hypersensitivity in a variety of rodent species. Elicitation of respiratory responses (immediate allergic, late allergic and dual-phase) however, occurs only via inhalation but not dermal exposure;

  • elicitation of respiratory responses can be demonstrated after exposures with MDI and with MDI-serum albumin conjugates. Cross-reactivity with other diisocyanates has been reported;

  • complex immunological mechanisms are involved in the sensitisation process.  Humoral as well as cellular immunity may be involved in the pathogenesis of hypersensitivity due to isocyanates;

  • short high-level exposure patterns appear to bear a higher sensitising potency than equal concentration × time (C x t) products at longer exposure periods;

  • Brown Norway (BN) rat MDI bioassay demonstrates the existence of a threshold for respiratory sensitisation following both skin and inhalation exposures. Several exposures well above the irritant threshold (so-called “lung-priming” exposures) are necessary as part of the induction process to enable respiratory sensitization in BN rats (Pauluhn, 2014a);

  • chemical-induced respiratory sensitization is likely to be contingent on two interlinked, sequential occurrences: first, dermal or inhalation exposures high enough to cause systemic sensitization; second, a subsequent supra-threshold irritant inhalation exposure(s), high enough to initiate and amplify an airway inflammation. A progression to respiratory sensitization (asthma) may follow.  

The Brown Norway (BN) rat model for respiratory sensitisation has used both dermal and inhalation routes for induction. The elicitation phase was typically four inhalation exposures, spaced at approximately 15-day intervals. After the last challenge, the measurements made included: respiratory responses using whole body plethysmography, analysis of inflammatory endpoints using lung lavage fluid and IgE levels in lung lavage fluid or serum. Lung and lymph node weights were measured post mortem and the respiratory tract was used for histopathological investigations. Controls did not receive the induction treatment but were challenged by inhalation as for the test groups, to control for short term irritation effects. On occasion respiratory methacholine challenge was performed the day following MDI challenge to test for non-specific respiratory hyperreactivity. The test material in these studies was pMDI.

Both inhalation and dermal routes of induction were investigated in a study using BN rats.  One group of animals was induced by dermal exposure (150μl neat pMDI on the flanks Day 0 and 75 µl neat pMDI on both ears Day 7) followed by inhalation challenge (4 x 30 min exposures to 15.7 mg/m3 pMDI on Days 21, 35, 50, and 64.) A second group of animals received an inhalation induction of 25-30 mg/m3 (5 x 3 hours/day) and the same subsequent challenge.  The dermally-induced animals demonstrated mild but consistent time-related increased BAL neutrophils and slightly increased lung and lymph-node weights. Lung histopathology revealed activated lymphatic tissue and an increased recruitment of airway eosinophils.  However, the inhalation-induced animals demonstrated a respiratory response on the initial challenge which was not seen subsequently and was assessed as reflex rather than an immune response. The determination of total IgE in serum did not reveal statistically significant differences between the groups. Conclusive route-of-induction related were not observed.  It was concluded that an allergic respiratory response was seen with topical induction and respiratory challenge (Pauluhn, 2005a; Pauluhn, 2005b). Subsequent studies used higher challenge concentrations to elicit a greater response.

A study to evaluate the  dose-response for the topical induction or inhalation challenge by pMDI was investigated using two protocols (Pauluhn, 2008a).  In the induction dose-response protocol, groups of eight BN rats were exposed by dermal induction to 2.5, 10 and 40μl/rat of neat pMDI  on days 0 and 7.  The test substance was applied as spots on aluminum foil to the shaved flank skin of the rats. The foil was pressed to the skin and removed, and the applied dose checked by weighing the foil. Each dose group consisted of three subgroups with varied dosed surface areas of 3.1-12.6 cm², 0.8-3.1 cm2, and 0.4-0.8 cm2, respectively. Inhalation challenges were made on days 20, 35, 50 and 65, using 38mg pMDI/m3 for 30 minutes. Controls included animals neither induced nor challenged and animals not induced but challenged four times. Post-challenge measurements of Penh focused and inflammatory endpoints in BAL were performed one day after the fourth challenge. Results indicated, with the exception of PMNs, most endpoints in BAL as well as lung or LALN weights did not demonstrate any remarkable dependence on the sensitization and challenge protocol applied. The elicited responses were essentially of the same magnitude across all treated groups, although most changes were statistically significantly different compared to the non-induced but challenged control group. In summary, it was not possible to establish the contribution of dose and surface area in the induction process.  A second protocol in the same study (Pauluhn, 2008a)  groups of BN rats were topically dosed with 40 mL of pMDI per rat followed by three challenges with 37 mg pMDI/m3 on days 20, 35 and 50. On day 65, the subgroups of rats were challenged with either 8, 18, or 39 mg pMDI/m3. There were 5 control groups which were not induced but were exposed to a single or repeated challenge. This protocol revealed that the elicitation dose correlates with increased neutrophils in BAL and delayed-onset respiratory responses. Based on the concentration-dependence of BAL-PMNs, 2.7 mg pMDI/m3 (81 mg MDI/m3 x min) is considered to be the threshold concentration to elicit respiratory responses in ‘‘asthmatic’’ rats. In summary, these data suggest that the vigor of asthma-like responses appear to be more dependent on the inhalation elicitation dose of previously challenged rats rather than the dermal induction dose.

The dose-response for inhalation induction by pMDI was investigated using inhalation induction at 3 different concentration x exposure time (C x t) values in BN rats, either at higher-concentration-shorter-duration or lower-concentration-longer-duration (Pauluhn and Poole, 2011). This study used a modified sensitization protocol of 5-day inhalation exposure (days 0-4) of Brown Norway (BN) rats to two C x t) relationships of 1000, 5000, and 10,000 mg pMDl/m3 x min at exposure durations of either 10 or 360-min.  This was followed by four 30-min inhalation challenges to 40 mg pMDl/m3 on target days 20, 25, 50, and 65. After the last challenge, changes in breathing patterns delayed in onset were recorded and allergic lung inflammation was probed by bronchoalveolar lavage (BAL). The high-concentration short-exposure duration sensitization protocol produced a significant and more vigorous elicitation response. In phase 2 of the study, groups of rats were sensitized using the 10-min C x t protocol and challenged 3-times at 40 mg pMDl/m3. At the fourth challenge a dose-escalation regimen of 5.1 or 14.5 or 39.8 mg pMDI/m3 was used to determine the elicitation threshold on 'asthmatic' rats. The lowest challenge concentration did not elicit a response, thus a no-effect level for the elicitation of 5 mg/m3 was demonstrated.

In addition to the studies in BN rats, data are available in guinea pigs:

  • In another key study, groups of guinea pigs were exposed to 4,4’-MDI by intradermal injection, topical application, or inhalation exposure for induction and by inhalation to 25-44 mg/m3 MDI for the challenge exposure. Attempts to sensitize guinea pigs by inhalation exposure to MDI were unsuccessful; no animals exhibited pulmonary responses following challenge with MDI. Intradermal injection or topical application of MDI induced specific antibody responses and pulmonary responses in 12-65 % of guinea pigs depending upon induction dose and route. The differences in immunogenicity observed clearly reflect variation in exposure route rather than the concentration of 4,4’-MDI used for sensitization (Rattray et al., 1994).

  • In a study, using intradermal induction, 12.5 % of the 4,4’-MDI sensitized guinea pigs showed a marked non-specific pulmonary reaction after an inhalation challenge of 35 mg/m3 4,4’-MDI which was not observed in sham or vehicle controls. An association between increased airway responsiveness, increased airway eosinophilia, and increased levels of IgG1 anti-MDI antibody titers could not be established (Pauluhn, 1994a).

  • In a study in guinea pigs using three intradermal and a single, nose only, 15-minute inhalation induction exposure followed on day 21 by a 30 min, nose only inhalation challenge to 3.4-60 mg/m3 4,4’-MDI or 35 mg/m3 4,4’-MDI-guinea pig serum albumin conjugate (MDI-GPSA), only 4,4’-MDI concentrations above the irritant threshold evoked a pronounced respiratory response. An increase in non-specific airway hyper-responsiveness was observed during acetylcholine-challenge in animals challenged previously with 60 mg/m³ 4,4’-MDI. Conclusive delayed onset respiratory responses were neither observed following the 4,4’-MDI nor the MDI-GPSA conjugate challenge. Respiratory responses were only provoked in animals challenged with overtly irritant MDI-concentrations (Pauluhn and Mohr, 1994). Another guinea pig study used an inhalation induction to 132 mg/m3 4,4’-MDI, nose only for 15 minutes and an inhalation challenge to 3, 15, and 35 mg/m3 MDI for 20 min/concentration for a total of 60 minutes on day 21. Only a borderline response was seen with this protocol. Mild 4,4’-MDI-specific immediate-onset responses were observed mainly during challenge to slightly irritant concentrations (35 mg/m³). A marked increase of neutrophilic or eosinophilic granulocytes could not be established. Animals sensitized to high concentrations of aerosolized MDI showed a mild airway hypersensitivity without concomitant influx of inflammatory cells (Pauluhn, 1995). An inter-laboratory study for the evaluation and validation of an animal model for low molecular weight chemicals to exhibit respiratory allergy in guinea pigs used intradermal induction of 0.0003 to 1 % and an inhalation challenge on day 22 to 18-55 mg/m3 MDI. The results demonstrated that the intradermal injection of MDI was able to induce high titre antigen-specific antibodies in guinea-pigs. Inhalation exposure to MDI, approximately three weeks after sensitisation with 4,4’-MDI, induced a pulmonary response characterized by changes in respiratory rate (Blaikie et al., 1995).

In summary, although there are no guidelines available for respiratory sensitization studies in animals, several researchers have shown respiratory changes in animals after induction exposure and subsequent challenge with both 4,4’-MDI and pMDI. The studies showed some type of respiratory response (alterations in respiratory rate, non-specific hyperreactivity, influx of inflammatory cells), however differences in immunogenicity observed clearly reflect variation in induction exposure route and/or challenge concentration. Attempts to sensitize guinea pigs by single inhalation exposure only to 4,4’-MDI showed borderline responses at best as compared with potent respiratory sensitizers such as ovaalbumin and trimellitic anhydride. Respiratory responses were only provoked in animals challenged with overtly irritant concentrations of 4,4’-MDI or pMDI.


Human information

There are clinical case reports of occupational diisocyanate asthma after initial exposure to presumably high concentrations of unspecified MDI substances. Occupational challenge tests or specific inhalation challenges have demonstrated asthmatic responses to low levels of MDI substances in sensitized individuals. Although antibody testing is appealing as a diagnostic tool, unlike high molecular weight agents, these serologic markers are insensitive and non-specific for disease detection (Ott et al., 2007).

An epidemiological study reported a reduction of absolute number of diisocyanate asthma cases more recently, compared to previous data in Canada (30 occupational asthma (OA) claims due to isocyanates (ISO)/year during 1980 to 1993 as compared to 7.4 ISO claims/year in 1998 to 2002) (Buyantseva et al., 2011).

A recent study in France has shown a significant decrease of work-related asthma over the period 2001–2009 for cases related with isocyanate exposures (Paris et al., 2012). In addition, a majority of diisocyanate asthma cases reported at least an improvement in respiratory symptoms at their last assessment; and 46 % reported clearing of all of their symptoms (Buyantseva et al., 2011). The isocyanate-related asthma incidence in Europe was reviewed by Poole (2013), who concluded that there was some indication of a downward trend in isocyanate associated occupational asthma in some countries, (i.e. France and Belgium), the number of cases in other countries remain steady, or possibly rising (Czech Republic). While tests are available to identify specific agents responsible for inducing the hypersensitive state, such testing is not applied in the majority of cases, with diagnosis relying on clinical examination and labour anamnesis. There is some indication that isocyanate occupational asthma might be associated with certain occupations/jobs using spray applications, but information is sparse. A cross-sectional study was performed with 243 employees exposed to MDI substances in a polyurethane processing facility. The 8-hour time weighted average exposures did not exceed 5 ppb, and all three cases diagnosed for work-related asthma appeared to have been induced as a result of intermittent high exposures during non-routine work activities (Bernstein et al., 1993). Overall, various recent data on isocyanate related asthma incidence indicates a reduction in cases in the last decade. Where controls and current exposure standards are met, new asthma cases can be minimized.

CLP regulation notes that evidence for chemical-induced respiratory sensitisation (asthma/rhinitis/conjunctivitis/alveolitis) will normally be based on human experience. This data can include “consumer experience and comments, preferably followed up by professionals (e.g. bronchial provocation tests, skin prick tests and measurements of specific IgE serum levels); records of workers’ experience, accidents, and exposure studies including medical surveillance; case reports in the general scientific and medical literature; consumer tests (monitoring by questionnaire and/or medical surveillance); epidemiological studies.” (ECHA, 2017a). As such, there is a large human dataset available that includes both case studies and epidemiological reports (Table 60). 

Major findings include:

  • MDI substances cause both immediate (seconds to minutes) and delayed-onset (up to several hours) type respiratory hypersensitivity in humans;

  • Humans exposed to MDI may suffer from a broad spectrum of respiratory effects not all related to respiratory sensitization, including respiratory irritation, aggravation of asthma and pathological changes of the airways;

  • Reported results suggest that relatively high peak concentrations can induce sensitisation, and that prevention of such concentrations will prevent workers from developing respiratory allergy;

  • There are clinical case reports of occupational diisocyanate asthma after initial exposure to presumably high concentrations of MDI substances. Occupational challenge tests or specific inhalation challenges have demonstrated asthmatic responses to low levels of MDI substances in sensitized individuals;

  • Epidemiological studies demonstrate that annual incidence of isocyanate-related occupational asthma has decreased concomitant with decreasing exposure levels, which is primarily driven by better industrial hygiene practices avoiding peak exposures;  

  • In addition, a majority of diisocyanate asthma cases reported at least an improvement in respiratory symptoms at their last assessment; and 46% reported clearing of all their symptoms (Buyantseva et al., 2011).


 Migrated from Short description of key information: 


MDI is a respiratory sensitizer which is indicated by human and animal data.


 Justification for selection of respiratory sensitisation endpoint: 


GLP compliant study with reliability 2, conducted according to the OECD-GD 39 (inhalation exposure methodology).





Justification for classification or non-classification

Skin sensitisation 


 According to Regulation (EC) No 1272/2008 (CLP) MDI is classified as skin sensitiser with Category 1 (H317: May cause an allergic skin reaction). 


 Respiratory sensitisation 


 According to Regulation (EC) No 1272/2008 (CLP) MDI is classified as respiratory sensitiser with Category 1 (H334: May cause allergy or asthma symptoms or breathing difficulties if inhaled). 

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